Metabolites in the regulatory risk assessment of pesticides in the EU

Abstract

A large majority of chemicals is converted into metabolites through xenobiotic-metabolising enzymes. Metabolites may present a spectrum of characteristics varying from similar to vastly different compared with the parent compound in terms of both toxicokinetics and toxicodynamics. In the pesticide arena, the role of metabolism and metabolites is increasingly recognised as a significant factor particularly for the design and interpretation of mammalian toxicological studies and in the toxicity assessment of pesticide/metabolite-associated issues for hazard characterization and risk assessment purposes, including the role of metabolites as parts in various residues in ecotoxicological adversities. This is of particular relevance to pesticide metabolites that are unique to humans in comparison with metabolites found in in vitro or in vivo animal studies, but also to disproportionate metabolites (quantitative differences) between humans and mammalian species. Presence of unique or disproportionate metabolites may underlie potential toxicological concerns. This review aims to present the current state-of-the-art of comparative metabolism and metabolites in pesticide research for hazard and risk assessment, including One Health perspectives, and future research needs based on the experiences gained at the European Food Safety Authority.

Synthetic approach to iodosulfuron-methyl and metsulfuron-methyl metabolites and their application for water analysis

“…A relative standard deviation of peak area for ten injections in one day for concentrations three different (25,200, and 500 ng mL −1 ) was calculated to determine intra-day precision. To determine inter-day precision between different days of operation, a relative standard deviation of peak area for ten injections per day at three different concentrations (25,200, and 500 ng mL −1 ) was calculated during the experiment's rst, third, and seventh days. The limit of quantication (LOQ) was determined as a signal/noise ratio of more than 10.…”

“… 24 The properties of these compounds have to be extensively surveyed to fully assess the safety of active substances. 25 Prompted by the commercial demand and recognizing that derivatives 3–13 are of limited availability, we decided to develop synthetic routes to these compounds. To show the utility of prepared compounds in environmental studies, we then used them as standards during the analysis of extracts from Vistula river water.…”